MARIBAVIR ISOMERS, COMPOSITIONS, METHODS OF MAKING AND METHODS OF USING

Abstract

The invention relates to novel compositions and methods of using maribavir which enhance its effectiveness in medical therapy, as well as to maribavir isomers and methods of use thereof for counteracting the potentially adverse effects of maribavir isomerization in vivo in the event it occurs.

Claims

1.-24. (canceled)

25. A method of treating a cytomegalovirus (CMV) infection in a patient having a CMV infection, the method comprising orally administering to the patient the compound 5,6-dichloro-2-(isopropylamino)-1-(?-L-ribofuranosyl)-1H-benzimidazole in an amount of 400 mg twice a day.

26. The method of claim 25, wherein said compound is administered to said patient with food.

27. The method of claim 25, wherein said compound is administered to said patient without food.

28. The method of claim 25, wherein said compound is administered as a composition comprising a therapeutically acceptable adjuvant, excipient, or carrier medium.

29. The method of claim 28, wherein said composition is an immediate release formulation.

30. A method for determining the therapeutic efficacy of the compound 5,6-dichloro-2-(isopropylamino)-1-(?-L-ribofuranosyl)-1H-benzimidazole, or an isomer of said compound in the blood plasma of a patient administered said compound, comprising measuring the concentration of a therapeutically effective form of said compound in a blood plasma sample from said patient and comparing said measured concentration with the concentration(s) of at least one of a lesser therapeutically effective form of said compound or an isomer or analog thereof in same patient sample.

31. The method according to claim 30, wherein said measurement and comparison is performed on patient samples during and within 12 hours of terminating treatment.

32. The method according to claim 30, wherein said measurement(s) and comparison(s) determine the treatment protocol of said patient.

33. The method according to claim 32, wherein said treatment protocol is the dosage amount of said compound administered to said patient, the dosage regimen for administration of said compound to said patient, the discontinuation of administration of said compound to said patient, or the initiation of other therapeutic intervention for said patient.

34. A composition comprising the compound 5,6-dichloro-2-(isopropylamino)-1-(?-L-ribofuranosyl)-1H-benzimidazole and at least one of an antacid which is effective for neutralizing acid that catalyzes isomerization of maribavir, an antibiotic having activity against a microorganism that mediates isomerization of maribavir and an antagonist that inhibits metabolism that induces isomerization of maribavir, said isomerization producing a decrease in the therapeutic efficacy of said compound.

35. The composition of claim 34, wherein the composition comprises an antacid which is effective for neutralizing acid that catalyzes isomerization of maribavir.

36. A method for treatment of a herpes viral infection in a patient in need thereof, wherein the patient is a stem cell transplant recipient, a kidney transplant recipient, or a liver transplant recipient, the method comprising orally administering to said patient the compound 5,6-dichloro-2-(isopropylamino)-1-(?-L-ribofuranosyl)-1H-benzimidazole, or an isomer of said compound, in an amount of 400 mg twice a day.

37. The method according to claim 36, wherein said compound comprises a pyranosyl analog of maribavir.

38. The method according to claim 37, wherein said pyranosyl analog of maribavir is selected from the group consisting of: ##STR00003## ##STR00004##

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0033] FIG. 1 shows chemical structures of maribavir and maribavir configurational stereoisomers that have the same configuration at the furanoysl anomer carbon.

[0034] FIG. 2 shows chemical structures of maribavir configurational stereoisomers that have the opposite configuration at the furanosyl anomer carbon.

[0035] FIG. 3 shows chemical structures of maribavir pyranosyl constitutional isomers)

[0036] A number of patent and non-patent documents are cited in the foregoing specification in order to describe the state of the art to which this invention pertains. The entire disclosure of each of these citations is incorporated by reference herein.

[0037] While certain of the preferred embodiments of the present invention have been described and specifically exemplified above, it is not intended that the invention be limited to such embodiments. Various modifications may be made thereto without departing from the scope and spirit of the present invention, as set forth in the following claims. Furthermore, the transitional terms comprising, consisting essentially of and consisting of define the scope of the appended claims, in original and amended form, with respect to what unrecited additional claim elements or steps, if any, are excluded from the scope of the claims. The term comprising is intended to be inclusive or open-ended and does not exclude additional, unrecited elements, methods step or materials. The phrase consisting of excludes any element, step or material other than those specified in the claim, and, in the latter instance, impurities ordinarily associated with the specified materials. The phrase consisting essentially of limits the scope of a claim to the specified elements, steps or materials and those that do not materially affect the basic and novel characteristic(s) of the claimed invention. All compositions or formulations identified herein can, in alternate embodiments, be more specifically defined by any of the transitional phases comprising, consisting essentially of and consisting of.